P
US9974828B2ActiveUtilityPatentIndex 83

Isoform nell-1 peptide

Assignee: UNIV CALIFORNIAPriority: Mar 25, 2009Filed: Sep 14, 2016Granted: May 22, 2018
Est. expiryMar 25, 2029(~2.7 yrs left)· nominal 20-yr term from priority
Inventors:TING KANGSOO CHIA
A61P 29/00A61K 35/32A61N 1/303A61P 19/10A61K 38/1709A61P 21/00C07K 14/47A61P 19/00A61M 37/0092A61M 2037/0007A61K 2300/00A61M 37/00A61K 48/0075A61K 48/005A61K 48/00
83
PatentIndex Score
4
Cited by
29
References
46
Claims

Abstract

This application is drawn to a method of using an isoform NELL-1 peptide, and compositions thereof for bone formation or for treating, preventing, or ameliorating osteoporosis.

Claims

exact text as granted — not AI-modified
We claim: 
     
       1. A method of increasing bone formation or regeneration in a subject in need thereof comprising administering to the subject a composition comprising an isolated polypeptide comprising a naturally occurring human, rat, or mouse neural epidermal growth factor-like (EGFL)-like-1 (Nell-1) polypeptide that extends from the beginning of the first chordin-like cysteine-rich domain to the end of the fifth chordin-like cysteine-rich domain, wherein the isolated polypeptide lacks the N-terminal thrombospondin-1 (TSP1) domain of a naturally occurring Nell-1 polypeptide. 
     
     
       2. The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
       3. The method of  claim 1 , wherein the composition further comprises a naturally occurring Nell-1 polypeptide. 
     
     
       4. A method of treating, preventing or ameliorating osteoporosis in a subject in need thereof comprising administering to the subject a composition comprising an isolated polypeptide comprising a naturally occurring human, rat, or mouse Nell-1 polypeptide that extends from the beginning of the first chordin-like cysteine-rich domain to the end of the fifth chordin-like cysteine-rich domain, wherein the isolated polypeptide lacks the N-terminal thrombospondin-1 (TSP1) domain of a naturally occurring Nell-1 polypeptide. 
     
     
       5. The method of  claim 4 , further comprising applying a physical force to bone tissue of the subject at a pre-selected site to disperse the composition. 
     
     
       6. The method  claim 4 , wherein the administering step comprises making an incision in bone tissue at a pre-selected site and delivering the composition to the bone tissue at the pre-selected site via the incision. 
     
     
       7. The method of  claim 5 , wherein the physical force is ultrasound. 
     
     
       8. The method of  claim 4 , wherein the composition is formulated for delivery by oral administration, topical administration, intravenous or intra-arterial administration, parenteral administration, in situ implantation, local administration, injection, percutaneous injection through intact skin to a site, direct injection through a surgically opened site or a trauma site, surgical implantation, extravascular delivery, extravascular injection, extravascular catheter based injection, intravascular delivery, intravascular injection, intravascular catheter based injection, intravenous delivery, intravenous injection, intravenous catheter based injection, intraarterial delivery, intraarterial injection, intraarterial catheter based injection, intrathecal delivery, intrathecal injection, intrathecal catheter based injection, intraosseous delivery, intraosseous injection, intraosseous catheter based injection, intracartilaginous delivery, intracartilaginous injection, intracartilaginous catheter based injection, intravesical delivery, intravesical injection, intravesical catheter based injection, a mechanical pump with a percutaneous or implantable catheter, catheter based delivery to an area or organ in the body, or expanded dispersion through a device that increases tissue penetration or promotes wider tissue distribution. 
     
     
       9. The method of  claim 8 , wherein the device provides ultrasound, iontophoresis, heat or pressure. 
     
     
       10. The method of  claim 4 , wherein the composition further comprises a synthetic bone graft material, a biocompatible matrix, a polymer, a bone morphogenic protein (BMP), collagen, or demineralized or mineralized bone powder or granules, or is combined with a prosthetic device. 
     
     
       11. The method of  claim 10 , wherein the biocompatible matrix comprises a cell expressing the isolated polypeptide. 
     
     
       12. The method of  claim 10 , wherein the synthetic bone graft material, biocompatible matrix, or polymer is resorbable. 
     
     
       13. The method of  claim 10 , wherein the polymer is a biodegradable polymer or a biostable polymer. 
     
     
       14. The method of  claim 10 , wherein the synthetic bone graft material, biocompatible matrix, or polymer comprises a cell adhesion molecule. 
     
     
       15. The method of  claim 10 , wherein the synthetic bone graft material comprises bioglass or a bioceramic. 
     
     
       16. The method of  claim 4 , wherein the composition is formulated for sustained release. 
     
     
       17. The method of  claim 4 , wherein the subject is a human. 
     
     
       18. The method of  claim 4 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
       19. The method of  claim 4 , wherein the composition further comprises a naturally occurring Nell-1 polypeptide. 
     
     
       20. The method of  claim 10 , wherein the BMP is BMP-2. 
     
     
       21. The method  claim 1 , wherein the administering step comprises making an incision in bone tissue at a pre-selected site and delivering the composition to the bone tissue at the pre-selected site via the incision. 
     
     
       22. The method of  claim 1 , wherein the composition is formulated for delivery by oral administration, topical administration, intravenous or intra-arterial administration, parenteral administration, in situ implantation, local administration, injection, percutaneous injection through intact skin to a site, direct injection through a surgically opened site or a trauma site, surgical implantation, extravascular delivery, extravascular injection, extravascular catheter based injection, intravascular delivery, intravascular injection, intravascular catheter based injection, intravenous delivery, intravenous injection, intravenous catheter based injection, intraarterial delivery, intraarterial injection, intraarterial catheter based injection, intrathecal delivery, intrathecal injection, intrathecal catheter based injection, intraosseous delivery, intraosseous injection, intraosseous catheter based injection, intracartilaginous delivery, intracartilaginous injection, intracartilaginous catheter based injection, intravesical delivery, intravesical injection, intravesical catheter based injection, a mechanical pump with a percutaneous or implantable catheter, catheter based delivery to an area or organ in the body, or expanded dispersion through a device that increases tissue penetration or promotes wider tissue distribution. 
     
     
       23. The method of  claim 22 , wherein the device provides ultrasound, iontophoresis, heat or pressure. 
     
     
       24. The method of  claim 1 , wherein the composition further comprises a synthetic bone graft material, a biocompatible matrix, a polymer, a BMP, collagen, or demineralized or mineralized bone powder or granules, or is combined with a prosthetic device. 
     
     
       25. The method of  claim 24 , wherein the BMP is BMP-2. 
     
     
       26. The method of  claim 24 , wherein the biocompatible matrix comprises a cell expressing the isolated polypeptide. 
     
     
       27. The method of  claim 24 , wherein the synthetic bone graft material, biocompatible matrix, or polymer is resorbable. 
     
     
       28. The method of  claim 24 , wherein the polymer is a biodegradable polymer or a biostable polymer. 
     
     
       29. The method of  claim 24 , wherein the synthetic bone graft material, biocompatible matrix, or polymer comprises a cell adhesion molecule. 
     
     
       30. The method of  claim 24 , wherein the synthetic bone graft material comprises bioglass or a bioceramic. 
     
     
       31. The method of  claim 1 , wherein the composition is formulated for sustained release. 
     
     
       32. The method of  claim 1 , wherein the subject is a human. 
     
     
       33. The method of  claim 1 , wherein the naturally occurring Nell-1 polypeptide has the sequence of SEQ ID NO: 3. 
     
     
       34. The method of  claim 4 , wherein the naturally occurring Nell-1 polypeptide has the sequence of SEQ ID NO: 3. 
     
     
       35. A method of increasing bone formation or regeneration in a subject in need thereof comprising administering to the subject a composition comprising an isolated polypeptide having an amino acid sequence with at least 93% sequence homology to a carboxy-terminal domain of a neural epidermal growth factor-like (EGFL)-like-1 (Nell-1) polypeptide having the amino acid sequence of SEQ ID NO:3, wherein the carboxy-terminal domain extends from the beginning of the first chordin-like cysteine-rich domain to the end of the fifth chordin-like cysteine-rich domain, and wherein the isolated polypeptide lacks the N-terminal thrombospondin-1 (TSP1) domain of the naturally occurring Nell-1 polypeptide. 
     
     
       36. The method of  claim 35 , wherein the composition is formulated for delivery by oral administration, topical administration, intravenous or intra-arterial administration, parenteral administration, in situ implantation, local administration, injection, percutaneous injection through intact skin to a site, direct injection through a surgically opened site or a trauma site, surgical implantation, extravascular delivery, extravascular injection, extravascular catheter based injection, intravascular delivery, intravascular injection, intravascular catheter based injection, intravenous delivery, intravenous injection, intravenous catheter based injection, intraarterial delivery, intraarterial injection, intraarterial catheter based injection, intrathecal delivery, intrathecal injection, intrathecal catheter based injection, intraosseous delivery, intraosseous injection, intraosseous catheter based injection, intracartilaginous delivery, intracartilaginous injection, intracartilaginous catheter based injection, intravesical delivery, intravesical injection, intravesical catheter based injection, a mechanical pump with a percutaneous or implantable catheter, catheter based delivery to an area or organ in the body, or expanded dispersion through a device that increases tissue penetration or promotes wider tissue distribution. 
     
     
       37. The method of  claim 35 , wherein the composition further comprises a synthetic bone graft material, a biocompatible matrix, a polymer, a BMP, collagen, or demineralized or mineralized bone powder or granules, or is combined with a prosthetic device. 
     
     
       38. The method of  claim 37 , wherein the BMP is BMP-2. 
     
     
       39. The method of  claim 37 , wherein the synthetic bone graft material, biocompatible matrix, or polymer is resorbable. 
     
     
       40. The method of  claim 37 , wherein the polymer is a biodegradable polymer or a biostable polymer. 
     
     
       41. The method of  claim 37 , wherein the synthetic bone graft material, biocompatible matrix, or polymer comprises a cell adhesion molecule. 
     
     
       42. The method of  claim 37 , wherein the synthetic bone graft material comprises bioglass or a bioceramic. 
     
     
       43. The method of  claim 35 , wherein the composition is formulated for sustained release. 
     
     
       44. The method of  claim 35 , wherein the subject is a human. 
     
     
       45. The method of  claim 35 , wherein the isolated polypeptide has the amino acid sequence of the carboxy-terminal domain of the Nell-1 polypeptide having the amino acid sequence of SEQ ID NO:3. 
     
     
       46. The method of  claim 35 , wherein the isolated polypeptide has the amino acid sequence of SEQ ID NO: 1.

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